HER2+ Breast Cancer Treatment Option | PERJETA® (pertuzumab) HCP

PROVIDE PERJETA^® (pertuzumab) + HERCEPTIN^® (trastuzumab)-BASED ADJUVANT TREATMENT FOR 1 FULL YEAR (UP TO 18 CYCLES)

PERJETA is indicated for use in combination with Herceptin and chemotherapy for the adjuvant treatment of patients with HER2+ early-stage breast cancer (EBC) at high risk of recurrence.¹

Visit the main PERJETA website

APHINITY: clinical trial design

PERJETA dosing: 840 mg loading dose, 420 mg for subsequent cycles; Herceptin dosing: 8 mg/kg loading dose, 6 mg/kg for subsequent cycles.

Investigators selected 1 of the following anthracycline-based or non–anthracycline-based chemotherapy regimens for individual patients:

3 or 4 cycles of FEC (5-fluorouracil 500-600 mg/m², epirubicin 90-120 mg/m², cyclophosphamide 500-600 mg/m²) or FAC (5-fluorouracil 500-600 mg/m², doxorubicin 50 mg/m², cyclophosphamide 500-600 mg/m²), followed by 3 or 4 cycles of docetaxel (75 mg/m², which could be escalated to 100 mg/m² every 3 weeks) or 12 cycles of weekly paclitaxel (80 mg/m²)
4 cycles of AC (doxorubicin 60 mg/m² and cyclophosphamide 500-600 mg/m²) or EC (epirubicin 90-120 mg/m² and cyclophosphamide 500-600 mg/m²) every 3 weeks or 2 weeks with GCSF support, followed by docetaxel (100 mg/m² for 3 cycles or 75 mg/m² for first cycle and 100 mg/m² for subsequent 3 cycles, or 75 mg/m² for 4 cycles) or 12 cycles of weekly paclitaxel (80 mg/m²)
6 cycles of docetaxel (75 mg/m²) in combination with carboplatin (AUC 6)

AUC=area under the curve; GCSF=granulocyte colony–stimulating factor.

Primary efficacy endpoint¹

Invasive disease–free survival (iDFS) defined as the time from randomization to the first occurrence of one of the following events:

Ipsilateral local or regional invasive breast cancer recurrence
Distant recurrence
Contralateral invasive breast cancer
Death from any cause

Secondary efficacy endpoints¹

iDFS, including second primary nonbreast cancer
Disease-free survival
Overall survival

APHINITY: patient demographics

Demographics were generally balanced between the two treatment arms¹

Select baseline patient characteristics table

The median age was 51 years (range, 18-86), 13% of patients were ≥65 years, and 71% were Caucasian¹
63% of patients had node-positive disease, and 64% had hormone receptor–positive disease¹
All patients had an ECOG performance status of 0 or 1¹
78% received an anthracycline-containing regimen¹

ECOG=Eastern Cooperative Oncology Group; ER=estrogen receptor; PR=progesterone receptor.

Adverse reaction (AR) profile from the APHINITY trial

*Denotes an AR that has been reported in association with a fatal outcome.

^†Primary cardiac events were defined as NYHA class III or IV and a substantial decrease in LVEF, or cardiac death, and were counted over the whole trial period, including post-treatment follow-up.

^‡A substantial decrease in LVEF is defined as a decrease of 10 or more percentage points, to a value <50%.

^§Secondary cardiac events were defined as asymptomatic or mildly symptomatic (NYHA class II) substantial decrease in LVEF, confirmed by a second LVEF assessment conducted within approximately 3 weeks also showing a substantial decrease or as confirmed by the cardiac advisory board, and were counted up to the date of recurrence or the end of post-treatment follow-up, whichever occurs first, in patients who have not had a primary cardiac event.

CI=confidence interval; LVEF=left ventricular ejection fraction; NYHA=New York Heart Association.

Diarrhea rates during chemotherapy and after it was discontinued^1,2

All Grades diarrhea during and after chemotherapy¹

Incidence of diarrhea when targeted therapy was administered with chemotherapy:
- 61% in the PERJETA-treated group
- 34% in the placebo-treated group
Incidence of diarrhea was higher when administered with non-anthracycline-based therapy vs with anthracycline-based therapy
Incidence of diarrhea during targeted therapy without chemotherapy:
- 18% in the PERJETA-treated group
- 9% in the placebo-treated group

Grades 3-4 diarrhea during and after chemotherapy

^‖Includes Grade ≥3 ARs with onset from first dose of any study treatment through 28 days after last dose of study treatment.²

^¶Includes Grade ≥3 ARs with onset during the targeted therapy post-chemotherapy treatment period.²

Patient selection

Assessment of HER2 protein overexpression and gene amplification should be performed using FDA-approved tests specific for breast cancer by laboratories with demonstrated proficiency.¹

Provide PERJETA + Herceptin-based therapy for a total of 1 year (up to 18 cycles)¹

Patients eligible to begin PERJETA and Herceptin-based therapy in the neoadjuvant setting¹

HER2+ locally advanced, inflammatory, or early breast cancer (EBC), node-positive, and/or tumor size >2 cm.

Neoadjuvant treatment regimen infographic

PERJETA dosing: 840 mg loading dose, 420 mg for subsequent cycles; Herceptin dosing: 8 mg/kg loading dose, 6 mg/kg for subsequent cycles.

Learn more about dosing and dose modifications.

Neoadjuvant chemotherapy regimens¹:

4 preoperative cycles of PERJETA in combination with Herceptin and docetaxel, followed by 3 postoperative cycles of FEC, as given in NeoSphere
3 or 4 preoperative cycles of FEC alone, followed by 3 or 4 preoperative cycles of PERJETA in combination with docetaxel and Herceptin, as given in TRYPHAENA and BERENICE, respectively
6 preoperative cycles of PERJETA in combination with docetaxel, carboplatin, and Herceptin (escalation of docetaxel above 75 mg/m² is not recommended), as given in TRYPHAENA
4 preoperative cycles of ddAC alone, followed by 4 preoperative cycles of PERJETA in combination with paclitaxel and Herceptin, as given in BERENICE

ddAC=dose-dense doxorubicin and cyclophosphamide; FEC=5-fluorouracil, epirubicin, and cyclophosphamide.

Patients eligible to begin PERJETA and Herceptin-based therapy in the adjuvant setting¹

HER2+ EBC at high risk of recurrence.

Adjuvant chemotherapy regimens¹:

3 or 4 cycles of FEC or FAC, followed by 3 or 4 cycles of docetaxel or 12 cycles of weekly paclitaxel
4 cycles of AC or EC either every 3 weeks or every 2 weeks with GCSF support, followed by 3 or 4 cycles of docetaxel or 12 cycles of weekly paclitaxel
6 cycles of docetaxel in combination with carboplatin

AC=doxorubicin and cyclophosphamide; EC=epirubicin and cyclophosphamide; FAC=5-fluorouracil, doxorubicin, cyclophosphamide; FEC=5-fluorouracil, epirubicin, and cyclophosphamide; GCSF=granulocyte colony–stimulating factor.

Dosing and dose modifications

Close observation of the patient is recommended for 30-60 minutes after each PERJETA infusion and before any subsequent infusion of Herceptin or chemotherapy.¹

Dose sequencing¹

PERJETA, Herceptin, and taxanes should be given sequentially
PERJETA and Herceptin can be given in any order
Taxane should be administered after PERJETA and Herceptin
In patients receiving an anthracycline-based regimen, PERJETA and Herceptin should be administered following completion of the anthracycline

Dose modifications¹

If a delayed or missed dose occurs¹

If the time between two sequential infusion cycles is <6 weeks, the 420 mg dose of PERJETA and the 6 mg/kg dose of Herceptin should be administered. Do not wait until the next planned dose
If the time between two sequential infusion cycles is ≥6 weeks, a reloading dose of PERJETA and Herceptin (840 mg and 8 mg/kg, respectively) should be administered

Dose interruption or discontinuation of treatment¹

PERJETA should be discontinued if Herceptin treatment is discontinued
Dose reductions are not recommended for PERJETA
For Herceptin and chemotherapy dose modifications, see their respective prescribing information
If a significant infusion-associated reaction occurs, slow or interrupt the infusion and administer appropriate medical therapies
The infusion should be discontinued immediately if the patient experiences a serious hypersensitivity reaction

Left ventricular ejection fraction (LVEF)

Assess left ventricular ejection fraction (LVEF) prior to initiation of PERJETA and at regular intervals during treatment to ensure that LVEF is within normal limits, as indicated below. If LVEF declines and has not improved, or has declined further at the subsequent assessment, discontinuation of PERJETA and trastuzumab should be strongly considered.

Dose modifications for left ventricular dysfunction

*For patients receiving anthracycline-based chemotherapy, an LVEF ≥50% is required after completion of anthracyclines, before starting PERJETA and Herceptin.

LVEF=left ventricular ejection fraction.

Cardiac monitoring during neoadjuvant and adjuvant treatment¹

PERJETA Prescribing Information

Get the latest Prescribing Information for PERJETA.

Download now

PERJETA Access Solutions

PERJETA Access Solutions is your resource for reliable, effective access and reimbursement support.

Find patient assistance

See other indications on PERJETA.com

Get more information about other PERJETA indications, resources for patients, and more.

Visit PERJETA.com

References

1.

PERJETA Prescribing Information. Genentech, Inc. 2018.

2.

von Minckwitz G, Procter M, de Azambuja E, et al. Adjuvant pertuzumab and trastuzumab in early HER2-positive breast cancer. N Engl J Med. 2017;377(2):122-131 and supplementary appendix.

3.

Herceptin Prescribing Information. Genentech, Inc. 2018.

Indication

PERJETA^® (pertuzumab) is indicated for use in combination with Herceptin^®(trastuzumab) and chemotherapy for

the neoadjuvant treatment of patients with HER2-positive, locally advanced, inflammatory, or early stage breast cancer (either greater than 2 cm in diameter or node-positive) as part of a complete treatment regimen for early breast cancer (EBC)

the adjuvant treatment of patients with HER2-positive early breast cancer (EBC) at high risk of recurrence

BOXED WARNINGS: Left Ventricular Dysfunction and Embryo-Fetal Toxicity

PERJETA can result in subclinical and clinical cardiac failure manifesting as decreased left ventricular ejection fraction (LVEF) and congestive heart failure (CHF). Evaluate cardiac function prior to and during treatment. Discontinue PERJETA treatment for a confirmed clinically significant decrease in left ventricular function

Exposure to PERJETA can result in embryo-fetal death and birth defects. Advise patients of these risks and the need for effective contraception

Based on its mechanism of action and findings in animal studies, PERJETA can cause fetal harm when administered to a pregnant woman. PERJETA is a HER2/neu receptor antagonist. Cases of oligohydramnios and oligohydramnios sequence manifesting as pulmonary hypoplasia, skeletal abnormalities, and neonatal death have been reported with use of another HER2/neu receptor antagonist (trastuzumab) during pregnancy. In an animal reproduction study, administration of pertuzumab to pregnant cynomolgus monkeys during the period of organogenesis resulted in oligohydramnios, delayed fetal kidney development, and embryo-fetal death at exposures 2.5 to 20 times the exposure in humans at the recommended dose, based on C_max
Verify the pregnancy status of females of reproductive potential prior to the initiation of PERJETA. Advise pregnant women and females of reproductive potential that exposure to PERJETA in combination with trastuzumab during pregnancy or within 7 months prior to conception can result in fetal harm, including embryo-fetal death or birth defects. Advise females of reproductive potential to use effective contraception during treatment and for 7 months following the last dose of PERJETA in combination with trastuzumab
There is a pregnancy-exposure registry that monitors pregnancy outcomes in women exposed to PERJETA during pregnancy. Encourage women who receive PERJETA in combination with trastuzumab during pregnancy or within 7 months prior to conception to enroll in the MotHER Pregnancy Registry by contacting 1-800-690-6720 or visiting http://www.motherpregnancyregistry.com/
If PERJETA is administered during pregnancy, or if a patient becomes pregnant while receiving PERJETA or within 7 months following the last dose of PERJETA in combination with trastuzumab, healthcare providers and patients should immediately report PERJETA exposure to Genentech at 1-888-835-2555

Left Ventricular Dysfunction (LVD)

Assess LVEF prior to initiation of PERJETA and at regular intervals during treatment to ensure that LVEF is within normal limits. If LVEF declines and has not improved, or has declined further at the subsequent assessment, discontinuation of PERJETA and trastuzumab should be strongly considered

In the NeoSphere study, for patients treated in the neoadjuvant setting, the incidence of left ventricular systolic dysfunction (LVSD) was higher in the PERJETA-treated groups compared to the trastuzumab and docetaxel–treated group. An increased incidence of LVEF declines was observed in patients treated with PERJETA in combination with trastuzumab and docetaxel. In the overall treatment period, LVEF decline >10% and a drop to <50% occurred in 2% of patients treated with neoadjuvant trastuzumab and docetaxel as compared to 8% of patients treated with neoadjuvant PERJETA in combination with trastuzumab and docetaxel. LVD occurred in 0.9% of patients treated with neoadjuvant trastuzumab and docetaxel as compared to 3% of patients treated with neoadjuvant PERJETA in combination with trastuzumab and docetaxel. Symptomatic LVSD occurred in 0.9% of patients treated with neoadjuvant PERJETA in combination with trastuzumab and in no patients in the other 3 arms. LVEF recovered to ≥50% in all patients

In the TRYPHAENA study, for patients treated in the neoadjuvant setting, in the overall treatment period, LVEF decline >10% and a drop to <50% occurred in 7% of patients treated with PERJETA plus trastuzumab and 5-fluorouracil, epirubicin, and cyclophosphamide (FEC), followed by PERJETA plus trastuzumab and docetaxel; in 16% of patients treated with PERJETA plus trastuzumab and docetaxel following FEC; and in 11% of patients treated with PERJETA in combination with docetaxel, carboplatin, and trastuzumab (TCH). LVD occurred in 6% of patients treated with PERJETA plus trastuzumab and FEC, followed by PERJETA plus trastuzumab and docetaxel; in 4% of patients treated with PERJETA plus trastuzumab and docetaxel following FEC; and in 3% of patients treated with PERJETA in combination with TCH. Symptomatic LVSD occurred in 4% of patients treated with PERJETA plus trastuzumab and docetaxel following FEC, in 1% of patients treated with PERJETA in combination with TCH, and in none of the patients treated with PERJETA plus trastuzumab and FEC, followed by PERJETA plus trastuzumab and docetaxel. LVEF recovered to ≥50% in all but 1 patient

In patients receiving neoadjuvant PERJETA in the BERENICE study, in the neoadjuvant period, LVEF decline ≥10% and a drop to <50% as measured by ECHO/MUGA assessment occurred in 7% of patients treated with PERJETA plus trastuzumab and paclitaxel following dose-dense doxorubicin and cyclophosphamide (ddAC), and in 2% of patients treated with PERJETA plus trastuzumab and docetaxel following FEC. Ejection fraction decrease (asymptomatic LVD) occurred in 7% of patients treated with PERJETA plus trastuzumab and paclitaxel following ddAC and in 4% of the patients treated with PERJETA plus trastuzumab and docetaxel following FEC in the neoadjuvant period. Symptomatic LVSD (New York Heart Association [NYHA] Class III/IV CHF) occurred in 2% of patients treated with PERJETA plus trastuzumab and paclitaxel following ddAC and in none of the patients treated with PERJETA plus trastuzumab and docetaxel following FEC in the neoadjuvant period

In the APHINITY study, for patients treated in the adjuvant setting, the incidence of symptomatic heart failure (NYHA Class III/IV) with a LVEF decline ≥10% and a drop to <50% was <1% (0.6% of PERJETA-treated patients vs 0.2% of placebo-treated patients). Of the patients who experienced symptomatic heart failure, 47% of PERJETA-treated patients and 67% of placebo-treated patients had recovered (defined as 2 consecutive LVEF measurements above 50%) at the data cutoff. The majority of the events (86%) were reported in anthracycline-treated patients. Asymptomatic or mildly symptomatic (NYHA Class II) declines in LVEF ≥10% and a drop to <50% were reported in 3% of PERJETA-treated patients and in 3% of placebo-treated patients, of whom 80% of PERJETA-treated patients and 81% of placebo-treated patients recovered at the data cutoff

Infusion-Related Reactions

PERJETA has been associated with infusion reactions, including fatal events

In the CLEOPATRA study, on the first day, when only PERJETA was administered, the overall frequency of infusion reactions was 13% in the PERJETA-treated group and 10% in the placebo-treated group. Less than 1% were Grade 3 or 4. The most common infusion reactions (≥1.0%) were pyrexia, chills, fatigue, headache, asthenia, hypersensitivity, and vomiting

In the NeoSphere, TRYPHAENA, and APHINITY studies, PERJETA was administered on the same day as the other study treatment drugs. For APHINITY, infusion-related reactions occurred in 21% of patients on the first day of PERJETA administration (in combination with trastuzumab and chemotherapy) and in 18% of patients in the placebo arm. The incidence of Grades 3-4 National Cancer Institute–Common Terminology Criteria for Adverse Events (NCI-CTCAE v4.0) reactions was 1% for the PERJETA arm and 0.7% for the placebo arm

Observe patients closely for 60 minutes after the first infusion and for 30 minutes after subsequent infusions of PERJETA. If a significant infusion reaction occurs, slow or interrupt the infusion and administer appropriate medical therapies. Monitor patients carefully until complete resolution of signs and symptoms. Consider permanent discontinuation in patients with severe infusion reactions

Hypersensitivity Reactions/Anaphylaxis

In the CLEOPATRA study, the overall frequency of hypersensitivity reaction/anaphylaxis was 11% in the PERJETA-treated group and 9% in the placebo-treated group. The incidence of Grades 3-4 hypersensitivity reaction/anaphylaxis was 2% in the PERJETA-treated group and 3% in the placebo-treated group according to NCI-CTCAE v3.0. Overall, 4 patients in the PERJETA-treated group and 2 patients in the placebo-treated group experienced anaphylaxis

In the NeoSphere, TRYPHAENA, BERENICE, and APHINITY studies, hypersensitivity/anaphylaxis events were consistent with those observed in CLEOPATRA. In NeoSphere, 2 patients in the PERJETA and docetaxel–treated group experienced anaphylaxis. In APHINITY, the overall frequency of hypersensitivity/anaphylaxis was 5% in the PERJETA-treated group vs 4% in the placebo-treated group. The incidence was highest in the PERJETA plus TCH–treated group (8%), of which 1% were NCI-CTCAE (v4.0) Grade 3-4

Patients should be observed closely for hypersensitivity reactions. Severe hypersensitivity, including anaphylaxis and fatal events, have been observed in patients treated within PERJETA. Angioedema has been described in post-marketing reports. Medications to treat such reactions, as well as emergency equipment, should be available for immediate use. PERJETA is contraindicated in patients with known hypersensitivity to pertuzumab or to any of its excipients

Neoadjuvant Treatment of Breast Cancer

The most common adverse reactions (>30%) with PERJETA in combination with trastuzumab and docetaxel administered for 4 cycles were alopecia, neutropenia, diarrhea, and nausea. The most common NCI-CTCAE v3.0 Grades 3-4 adverse reactions (>2%) were neutropenia, febrile neutropenia, leukopenia, and diarrhea

The most common adverse reactions (>30%) with PERJETA in combination with trastuzumab and docetaxel administered for 3 cycles following 3 cycles of FEC were diarrhea, nausea, alopecia, neutropenia, vomiting, and fatigue. The most common NCI-CTCAE v3.0 Grades 3-4 adverse reactions (>2%) were neutropenia, leukopenia, febrile neutropenia, diarrhea, left ventricular dysfunction, anemia, dyspnea, nausea, and vomiting

The most common adverse reactions (>30%) with PERJETA in combination with TCH administered for 6 cycles were diarrhea, alopecia, neutropenia, nausea, fatigue, vomiting, anemia, and thrombocytopenia. The most common NCI-CTCAE v3.0 Grades 3-4 adverse reactions (>2%) were neutropenia, febrile neutropenia, anemia, leukopenia, diarrhea, thrombocytopenia, vomiting, fatigue, alanine aminotransferase (ALT) increased, hypokalemia, and hypersensitivity

The most common adverse reactions (>30%) with PERJETA in combination with trastuzumab and paclitaxel administered for 4 cycles following 4 cycles of ddAC were nausea, diarrhea, alopecia, fatigue, constipation, peripheral neuropathy, and headache. The most common Grades 3-4 adverse reactions (>2%) were neutropenia, febrile neutropenia, neutrophil count decreased, white blood cell count decreased, anemia, diarrhea, peripheral neuropathy, ALT increased, and nausea

The most common adverse reactions (>30%) with PERJETA in combination with trastuzumab and docetaxel administered for 4 cycles following 4 cycles of FEC were diarrhea, nausea, alopecia, asthenia, constipation, fatigue, mucosal inflammation, vomiting, myalgia, and anemia. The most common Grades 3-4 adverse reactions (>2%) were febrile neutropenia, diarrhea, neutropenia, neutrophil count decreased, stomatitis, fatigue, vomiting, mucosal inflammation, neutropenic sepsis, and anemia

Adjuvant Treatment of Breast Cancer

The most common adverse reactions (>30%) with PERJETA in combination with trastuzumab and chemotherapy were diarrhea, nausea, alopecia, fatigue, peripheral neuropathy, and vomiting. The most common Grades 3-4 adverse reactions (>2%) were neutropenia, febrile neutropenia, diarrhea, neutrophil count decreased, anemia, white blood cell count decreased, leukopenia, fatigue, nausea, and stomatitis

The incidence of diarrhea, all Grades, was higher when chemotherapy was administered with targeted therapy (61% in the PERJETA-treated group vs 34% in the placebo-treated group) and was higher when administered with non–anthracycline-based therapy (85% in the PERJETA-treated group vs 62% in the placebo-treated group) than with anthracycline-based therapy (67% in the PERJETA-treated group vs 41% in the placebo-treated group). The incidence of diarrhea during the period that targeted therapy was administered without chemotherapy was 18% in the PERJETA-treated group vs 9% in the placebo-treated group. The median duration of all Grades diarrhea was 8 days for the PERJETA-treated group vs. 6 days for the placebo-treated group. The median duration of Grade ≥3 diarrhea was 20 days for the PERJETA-treated group vs. 8 days for the placebo-treated group. More patients required hospitalization for diarrhea as a serious adverse event in the PERJETA-treated group (2.4%) than in the placebo-treated group (0.7%)

You may report side effects to the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at 1-888-835-2555.

Please see full Prescribing Information for additional Important Safety Information, including BOXED WARNINGS.

Patient Eligibility

Adjuvant patient eligibility¹

Trial Design